Endocrine Abstracts

Introduction: Leptin is a pro-inflammatory cytokine and excess leptin in obesity may induce autoimmune disease. The suppressors of cytokine signalling (SOCS) are negative regulators of cytokine signalling and therefore a target for therapy. SOCS3 modulates leptin actions but there is no data regarding other SOCS proteins and leptin signalling.Aim: To develop a bioassay and examine the actions of SOCS proteins on leptin signalling.M...

The mechanisms which control the cell cycle and growth of adrenocortical cells remain largely uncharacterized. ACTH binds to its G protein-coupled receptor (GPCR), the melanocortin 2 receptor (MC2R) in the adrenal cortex and mediates the production of cAMP resulting in steroidogenesis. ACTH however also remains a candidate for the control of growth in the adrenal cortex. It is well known to have a growth promoting effect in vivo but has an opposing effect in some cell systems ...

Background Somatostatin has various biological effects such as modulation of exocrine and endocrine secretions, proliferation and apoptosis. These effects have been shown to be mediated via G-protein linked receptors known as somatostatin receptors 1-5 (SST 1-5). It has been shown that SST 2 in particular can be modulated by estrogen. The phytoestrogen genistein acts through the estrogen receptor beta and has been shown to have opposing effects on cell proliferation at differe...

Background Somatostatin has many putative biological effects in the kidney such as influencing renal blood flow and urine volume, tubular transport and cell regulation. It exerts these effects via five identified G-protein linked receptors. However, only somatostatin receptor proteins 1 and 2A have been described in human kidney so far. In this study, we examined the distribution of somatostatin receptors (SSTRs) in normal human adult kidney. Methods Formalin fixed paraffin em...

INTRODUCTION: We have been interested to investigate the biological activity of mutant molecules of growth hormone. Purification of growth hormone requires multiple steps. We have investigated a method to purify growth hormone which would be applicable to most protein hormones that bind to cell surface receptors.AIM: To test whether his-tagged extracellular domain growth hormone receptor could be used to purify recombinant growth hormone.<p class="ab...

The anti-inflammatory actions of glucocorticoids are mediated in part by inhibition of nuclear factor kappa B (NFkappaB) activation. Reports that NFkappaB activation within anterior pituitary folliculo-stellate (FS) cells provokes the release of interleukin-6 (IL-6) [1] which acts a paracrine mediator of ACTH release [2], raise the possibility that NFkappaB is a potential target for the negative feedback actions of glucocorticoids upon the hypothalamo-pitu...

PCOS is the most common endocrine disorder of premenopausal women. The in utero testosterone-treated ewe shares several key features with PCOS women (sub/infertility, multi-follicular ovaries, hypersecretion of gondotrophins and androgens) and, therefore, may be a useful animal model for this condition. In addition to reproductive abnormalities, PCOS women are at increased risk of hyperinsulinaemia and insulin resistance. The aim of this study was to determine if similar metab...

Kisspeptin is the peptide product of the KiSS-1 gene and endogenous agonist for the GPR54 receptor. The kisspeptin/GPR54 system has recently been suggested as a key regulator of the reproductive system. GPR54 deficient mice have abnormal sexual development and low circulating gonadotrophins and in humans, GPR54 mutations have been shown to cause hypogonadotrophic hypogonadism. Thus, GPR54 appears to be essential for normal gonadotrophin secretion and the regulation of puberty....

The major source of neurokinin B (NKB), a peptide of the tachykinin family, is the placenta. Little is known of the regulation of NKB or its preferred hypertensive-inducing receptor, NK3, during pregnancy, nor, the mechanisms leading to elevated NKB associated with pre-eclampsia (PE) during the third trimester. Using the pregnant rat we have looked at the changes in NKB and NK3 expression using real time PCR between day 16 and 21 of gestation in the placenta, brain and differe...

Macroprolactin, a circulating complex of monomeric prolactin together with an autoantibody, is commonly encountered in the course of endocrine investigations. It is generally agreed macroprolactin exhibits reduced bioactivity in vivo since individuals who harbour the complex do not demonstrate the classic clinical signs or symptoms characteristic of true hyperprolactinaemia. The aim of this study was to compare the relative potency of purified preparations of macroprolactin to...

Approximately 90% of ovarian cancers are derived from ovarian surface epithelial (OSE) cells and are believed to result from repeated episodes of ovulation-associated injury and repair. A knowledge of the control of OSE cell survival is therefore of major interest regarding our understanding of ovarian cancers. We have previously demonstrated that CREB protein is activated in OSE cells around pre-ovulatory follicles and suggested that this activation may play a role to promote...

Seminal vesicles play important roles in male infertility due to their secretions and contractile properties. Beside their sympathetic and parasympathetic nerve supply, seminal vesicles are also innervated by purinergic stimuli. Additionally, prolactin affects the gonadal, seminal vesicle, prostate functions and contributes to seminal plasma and sexual function. Medical treatment of hyperprolactinemia usually involves dopamine agonists. In the present study, effects of treated...

Efficiency of superovulatory protocols in ruminants is affected by occurrence of several reproductive abnormalities, such as anovulatory follicles (Kafi and McGowan 1997, Animal Reproduction Science, 48:137-157). The aims of current study were to characterize, in sheep, the incidence and possible causes of anovulatory follicles, their endocrine functionality in terms of oestradiol production and possible effects on viability of embryos from other follicles. The number and size...

Synthesis of thyroid hormones by the fetal thyroid requires the passage of iodide through the placenta. In the thyroid active iodide transport is facilitated by three transporters, the sodium iodide symporter (NIS), Pendrin (PDS) and the recently described the human apical iodide transporter (hAIT). Simultaneous expression of all three transporters appears to be thyroid restricted and although extrathyroidal expression of individual transporters has been reported, relatively l...

Nebivolol is a recently developed beta(1)-selective adrenergic receptor antagonist with proposed nitric oxide mediated vasodilating properties. Effect of nebivolol on vascular smooth muscle has been attributed to estrogen receptor-mediated vascular responsiveness. Although it is known that nitric oxide has relaxing effect on myometrium, there is no report whether nebivolol application affect myometrial contractility. Therefore, we have investigated the effect of nebivolol on r...

BackgroundThere is a need to develop a highly sensitive and reliable immunoassay method for the determination of testosterone concentrations both in children and adults. Testosterone in blood is largely bound to proteins (sex hormone binding globulin and albumin). The unbound fraction of testosterone is considered to be the biologically active hormone which correlates more closely with the physiologically effective level of this hormone. It is postulated...

Where screening for macroprolactin takes place, laboratories routinely rely on treatment of sera with polyethylene glycol (PEG) to distinguish macroprolactinaemia from true hyperprolactinaemia. However, PEG is incompatible with a number of common immunoassay platforms. The aim of this study was to assess the specificity and clinical utility of ultrafiltration as an alternative procedure for removal of bio-inactive prolactin IgG complexes such as macroprolactin from serum prior...

Systematic collections of neuroimaging data are rare in brain tumour survivors treated with adult growth hormone replacement therapy (AGHRT). In 1993, our unit implemented a policy of performing baseline brain scans on every brain tumour survivor before starting AGHRT, with repeat neuroimaging at least once after 12 to 18 months treatment. This retrospective study analyses the neuroimaging results for this cohort of 60 patients. Follow-up scans were available in 41 (91%) of th...

Adult growth hormone replacement is currently given by daily sc injections in the vast majority of children and adults treated for growth hormone (GH) deficiency. In recent years, sustained-release preparations of GH have been developed; the preparations available so far maintained therapeutic GH concentrations for approximately 14 days, but were characterised by a dominant early release, which resulted in high supraphysiological early GH peaks, and a rapid decline thereafter....

CDGP is a common growth disorder, often dominantly inherited. Genetic association is thus very likely. There are many possible candidates but none are yet linked to CDGP. We assessed the possible contribution of L, LR genes (mutations in each cause very delayed or absent puberty), CART (mediates the effect of L on GnRH pulse generation), and GPR54 (a hypothalamic G-protein coupled receptor, which is mutated in familial hypogonadotrophic hypogonadism) genes.<p class="abstex...

Background: Obese subjects are usually in a positive energy balance despite their best efforts to lose weight. This study aimed to determine if hunger, nausea and satiety levels differ in lean and obese subjects after consuming varying calorific meals.Method: Following an overnight fast, test meals of 250, 500, 1000, 2000 and 3000 kcal were consumed by 19 lean and 19 obese subjects. Hunger, nausea and satiety levels were measured using visual analogue sc...

One study examining the lipid profile of adults with partial GH deficiency (GH insufficiency, GHI) suggested they are dyslipidaemic. We defined GH status using two stimulation tests, the ITT and AST, in to patients with severe GHD (pGH < 3ng/ml, n = 30) or GHI (pGH 3 - 7ng/ml, n = 24). Thirty age and gender matched controls were studied.There were no differences in age between the GHD, GHI, and control subjects (30.9 vs 31.5 vs 34.2 yrs). IGF-I levels...

Objectives: Patients with acquired growth hormone (GH) deficiency secondary to hypopituitarism, have a significant increased risk of cardiovascular events. However, variable data of the effects of GH replacement and its benefits reducing such risk, is available. The aim of this study was to determine the impact of 0.4 milligrams of GH on cardiovascular markers in severe GH deficient adults with hypopituitarism.Methods: A total of 17 patients (10 males an...

Growth hormone insensitivity, also known as Laron Syndrome (LS), is caused by mutations within the GH receptor (GHR). A 1.5 year-old boy with consanguineous parents was referred with postnatal linear growth failure (length 64 cms, minus 6 SDS). Facial features were typical of LS. Investigation revealed elevated serum GH (1145 mIU per litre) and low IGF-I (4 nmol per litre). Genomic DNA was isolated from peripheral blood leucocytes and all GHR exons, including intron-exon bound...

During early development, the extravillous and villous placenta form by a process of proliferation and differentiation resulting in invasion of the uterine decidua and myometrium. The invasion of tissues during placentation is a model for the proliferative and invasive processes which occur during tumourogenesis. Pituitary tumor transforming gene (PTTG) interacts with a binding factor PBF, and PTTG expression correlates with tumor invasiveness in many neoplasms. We hypothesise...

Studies on the lipid emulsion for total parenteral nutrition (TPN) for the premature human infant are limited. We investigated the effects of modifying the fatty acid composition of TPN on the growth and development of the preterm piglet.Piglets delivered by Caesarean section on day 112 of gestation (term = 115 days) received an enteral diet (E: n=6) or TPN solution plus Intralipid (54% 18:2, 25% 18:1; I: n=6) or ClinOleic (17% 18:2, 65% 18:1; C: n=6) fo...

During mitosis, temporal release of separase from its inhibitor securin results in cohesin cleavage, thereby promoting anaphase. The developing fetal brain has rapidly proliferating neuronal cells whilst adult neurons no longer proliferate. When comparing 61 fetal and 12 adult human brain samples, we found significantly increased separase mRNA and protein throughout ontogeny and reduced securin expression in fetal brain compared with adult. Using MTT assays, we examined the ef...

Low birth weight infants have higher mortality rates and are at a greater risk of impaired immunity in later life than are their normal-birth-weight counterparts. The aim was to investigate the effect of maternal dietary fat supplementation during the first or second half of gestation on the plasma immunoglobulin A concentration in her offspring.Six pregnant sows were randomly allocated to receive 10% extra energy derived from dietary fat during either t...

Background - Adverse fetal nutritional supply results in programmed endothelial dysfunction and hypertension in offspring. Nitric Oxide Synthase (eNOS), Endothelin-1 (ET-1), and human Cationic Amino acid Transporter-1 (hCAT-1) are key players in endothelial function. We have shown that hCAT-1 is down-regulated in smaller neonates. One possible explanatory mechanism is DNA methylation, which reduces gene expression. In mice and rat models maternal diets with altered leve...

PTH plays an important role in bone metabolism. Active acromegaly is associated with increased bone turnover. Reduction in bone turnover markers occurs following biochemical cure/control of acromegaly. We examined the effect of active acromegaly and its treatment on PTH concentration and PTH target-organ sensitivity.10 patients with active acromegaly (defined as GH nadir greater than 1mU/L following 75g oral glucose load and IGF1 above reference range) a...

BACKGROUD: Parathyroid hormone (PTH) is normally secreted in a circadian rhythm and modulates bone turnover through the differential stimulation of receptor activator for nuclear factor kappa-B ligand (RANKL) and suppression of osteoprotegerin (OPG), both of which are fundamental factors in regulating bone turnover. We have studied the relationship between PTH and OPG over a 24-hour period.METHODS: Hourly peripheral venous blood samples were obtained fro...

Aims and MethodsBone density (BMD) measurement is essential to assess the skeletal impact of primary hyperparathyroidism (PHPT). Coexistent osteoporosis is one of the criteria to consider parathyroidectomy in PHPT. PHPT is associated with predominant bone loss at the wrist. Assessment of BMD at this site is important to identify all patients with osteoporosis. Repeat BMDmeasurements are imperative to assess progression of disease, response to treatment a...

Adult Growth Hormone Deficiency (AGHD) is associated with relative phosphate deficiency. Phosphate is an important determinant of serum PTH concentration. PTH target-organ sensitivity is reduced in AGHD and may underlie the pathogenesis of AGHD-related osteopaenia. We examined the effect of phosphate supplementation on change in PTH target-organ sensitivity when given simultaneously with Growth Hormone Replacement (GHR) in AGHD patients.24 AGHD patients ...

Raloxifene is a new selective estrogen modulator. It has been shown to prevent bone loss and to reduce vertebral fracture risk in postmenopausal women. This study was designed to investigate effects of raloxifene and oestradiol on bone formation and resorption in intact and ovariectomized (ovx) rat models. In the intact model, a total of 24 adult female rats were divided into three groups: Controls subcutaneously received saline alone. Raloxifene (2 mg/kg) and oestradiol (30 m...

Polychlorinated biphenyls (PCBs) are persistent environmental pollutants. Two industrial PCB mixtures, Aroclors 1221 and 1254 have been suggested to have estrogenic and anti-estrogenic properties, respectively. We have examined whether these PCB mixtures modulated bone formation and resorption in intact and ovariectomized (ovx) rat models. Twentyfour adult female rats were divided into three groups subcutaneously receiving 4% DMSO (Control), Aroclor 1221 (10 mg/kg) and Aroclor...

Objective: To study the protective effect of grape procyanidins on hydrogen peroxide induced oxidative damage in MC3T3-E1 osteoblast-like cells. Methods: Cultured MC3T3-E1 Osteoblast-like cells were treated with grape procyanidins and 125 micromole per litre hydrogen peroxide for six hours. The levels of apoptosis, mitochondrial transmembrane potential and proliferation were subsequently analyzed by flow cytometry and Bio-Red model 550 instrument. Results: The proliferation le...

Glucocorticoids (GCs) are important therapeutic agents for a wide-variety of inflammatory diseases but are known to have potentially detrimental side-effects such as osteoporotic bone-loss. These effects of GCs are mediated via the intracellular GC receptor (GR) and by local GC metabolism catalyzed by 11beta-hydroxysteroid dehydrogenase (11beta-HSD). We have postulated that autocrine activation of GCs via 11beta-HSD1 plays a key role in counteracting the effects of inflammator...

This study was designed to investigate effects of raloxifene treatment on serum interleukin (IL)-4 and transforming growth factor-beta (TGFbeta)1 concentrations in healthy postmenopausal women. The study was approved by the local ethics committee. Thirty five women were enrolled into this study and randomly divided in two groups. While 16 women were included in raloxifene group, control group was comprised of remaining 19 women. The study group continuously received 60 mg ralo...

It has recently been shown that loss-of-function mutations of the G protein coupled receptor GPR54 lead to isolated hypogonadotropic hypogonadism (IHH) in mice and humans. Such mutations are thought to be rare, even within the clinical IHH population, and only a handful of alleles have been described, making further screening of IHH populations imperative. We examined the genes encoding GPR54 and its putative endogenous ligand, kisspeptin-1, for mutations in a cohort of 30 pat...

Backround: Recent research has heightened the controversy surrounding the effects of conventional hormone replacement therapy on cardiovascular risk, suggesting that use of HRT is associated with an increase in cardiovascular morbidity and mortality. Testosterone has also been associated with unfavourable cardiovascular parameters and the addition of testosterone to HRT may augment the risk of cardiovascular events in postmenopausal women.Aim: To elucida...

The relationship of insulin resistance, androgens and endothelial dysfunction in polycystic ovary syndrome ,PCOS, is controversial till now. We evaluated if ICAM-1 levels differ between PCOS and healthy women and whether this marker of the early endothelial damage is associated with the particular metabolic and/or hormonal characteristics.After signing written informed consent, 39 PCOS women -median of age 25 yrs, BMI 24.9 and 10 age matched healthy wome...

The A-3826G gene polymorphism of the uncoupling protein 1 (UCP1) causes the lower expression of UCP1 in visceral fat and reduced energy expenditure. Peroxisome proliferator activated receptor gamma 2 (PPARG2) plays a role in the regulation of the adipocyte differentiation and energy balance. The Pro12Ala polymorphism is associated with better insulin sensitivity. We compare the genotypic distribution of these polymorphisms in PCOS and controls and study their possible associat...

BackgroundTransdermally absorbed alcohol-based testosterone gel has presented an alternative method of gonadal therapy. This study was designed to investigate the clinical effectiveness of this alternative hormonal replacement.Method97 men requiring testosterone replacement therapy for primary (21%) or secondary (79%) hypogonadism were recruited. The subjects underwent physical examination, psychological asse...

Objective: PCOS affects approximately 10% of women of reproductive age. We have audited the management of women attending the multidisciplinary PCOS clinic at the Royal Berkshire Hospital which was set up in September 2002.Methods: Data on women attending the PCOS clinic at the Royal Berkshire Hospital between September 2002 and September 2004 were analysed. Points investigated were: baseline characteristics, adequacy of investigations and efficacy of tr...

There has been controversy over the diagnostic utility of the LH/FSH ratio in polycystic ovarian syndrome, with more recent guidelines excluding it as a diagnostic test. However, LH/FSH is still often requested for that purpose and in our institution, 20% of the 12,000 annual requests for LH/FSH tests requested in a one year period had PCOS detailed on the card, at a cost of over £37,000.Objective: The aim of this study was to ascertain the biologi...

BackgroundThis study was designed to monitor the clinical effectiveness of transdermal replacement. Psychological well-being was assessed by questionnaire at 3, 6 and 12MethodWe recruited 97 men requiring testosterone replacement therapy for primary (21%) or secondary (79%) hypogonadism. All had a physical examination, biochemical and haematological blood sampling (Meston et al 2004) and psychological assessm...

Recognition of male adult onset hypogonadotrophic hypogonadism (HH) is important in identifying treatable forms of infertility, erectile dysfunction and osteoporosis.There are currently no evidence-based guidelines for diagnosing and treating HH.We evaluated the assessment, diagnosis, treatment strategies and outcome in adult men with suspected HH seen in our endocrine clinic over 1 year. We aimed to evaluate the usefulness of pitu...

Macroprolactin is a high molecular mass prolactin isoform found in some normal individuals. The most common form of macroprolactin arises from binding of prolactin to IgG ('big-big' prolactin), with a molecular mass 150-170 kD. A further prolactin isoform of intermediate size ('big' prolactin, 50-60 kD), has also been described but the nature and significance of this form is less clearly understood.We have previously described the effects of pregnancy in...